There are conflicting results concerning the receptor subtype(s) involved in calcium-mediated endothelin signaling in the glial cells. In order to elucidate the role of endothelin A and B receptors in these processes, we have studied the effect of a complex spectrum of endothelin receptor ligands on intracellular calcium concentration changes in proliferating and differentiated C6 rat glioma cells. Cell differentiation was induced by dibutyryl-cAMP and assessed by the glial fibrillar acidic protein content. Intracellular calcium changes were measured in cell suspensions using fluorescent probe Fura-2. The specific endothelin B receptor agonists sarafotoxin S6c and IRL-1620 did not influence the intracellular calcium concentration. However, calcium changes induced by endothelin-1 and especially by endothelin-3 after the pretreatment of cells with one of these endothelin B receptor specific agonists were significantly enhanced even above the values attained by the highest effective endothelin concentrations alone. Such endothelin B-receptor ligand-induced sensitization of calcium signaling was not observed in differentiated C6 cells. Moreover, endothelin-induced calcium oscillations in differentiated C6 cells were less inhibited by BQ-123 and BQ-788 than in their proliferating counterparts. In conclusion, the specific activation of endothelin B receptor in C6 rat glioma cells does not affect intracellular calcium per se, but probably does so through interaction with the endothelin A receptor. The pattern and/or functional parameters of endothelin receptors in C6 rat glioma cells are modified by cell differentiation., R. Malík, K. Vlašicová, A. Šedo., and Obsahuje bibliografii
It has been shown that nitric oxide (NO) increases aggression in male mice, whereas it decreases aggression in lactating female mice and prairie voles. It is also known that aggression can be exhibited at different levels in rodent species, strain or subtypes. The aims of this study were to investigate the proportion of aggressiveness in Wistar rats, the effect of intraperitoneally administered nonspecific nitric oxide synthase (NOS) inhibitor L-NAME (NG-nitro L-arginine methyl ester) on maternal aggression towards female intruders, and whether these effects are due to NO production or not. Rats were given saline intraperitoneally on the postpartum Day 2 and aggression levels were recorded. The same rats were given 60 mg/kg L-NAME or D-NAME (NG-nitro D-arginine methyl ester) on the postpartum Day 3 and their effects on aggression levels were compared to saline. While L-NAME administration did not cause any differences in the total number of aggressive behavior, aggression duration and aggression intensity, it reduced the proportion of animals showing aggressive behavior. In addition, the latency of the first aggression was significantly increased by L-NAME. In the D-NAME group, however, no significant change was found. Our results have shown that L-NAME reduces maternal aggression towards female intruders in Wistar rats through inhibition of NO production. These results suggest that the role of NO in offensive and defensive maternal aggression shares neural mechanisms., S. Ankarali, H. C. Ankarali, C. Marangoz., and Obsahuje seznam literatury
Gender is presumed to be one of the factors causing interindividual variability in the brain’s electrophysiological parameters. Our aim was to characterize the role of gender in visual evoked potentials (VEPs), event-related potentials (ERPs), visual mismatch negativity (vMMN) and the spectral characteristics of the EEG. We examined 42 healthy volunteers (21 women and 21 men, aged 20-29 years). We measured VEPs in response to pattern-reversal and motion-onset stimulation, ERPs in an oddball paradigm and vMMN in response to a combination of motion directions presented in the visual periphery. P100 peak latency for 40’ reversal VEPs was significantly shorter in women than in men as determined using a non-parametric Wilcoxon signed-rank test. In addition, women showed higher relative EEG spectral power in the alpha band (p=0.023) and lower power in the theta band (p=0.004). Our results in this small but homogeneous group of subjects confirm previously reported gender influences on pattern-reversal VEPs and the EEG frequency spectrum. Gender should be taken into consideration in establishing norms on these measures. We found no statistically significant differences between women and men for any of the other stimuli presented., J. Langrová, ... [et al.]., and Obsahuje seznam literatury
Genetic strain-dependent reactivity to mechanical stimuli in rat skeletal muscle has not been examined. This study aimed to examine whether genetic strain-dependency is associated with reactivity in protein metabolism and the resultant muscle hypertrophy after isometric resistance training (RT). The right triceps of Sprague-Dawley (SD) and Wistar rats underwent 12 sessions of RT. After RT, a transition from the IIb to the IIx myosin heavy-chain isoform was observed in both strains. In SD rats, the lateral gastrocnemius muscle (LG) mass of the trained legs (TRN) was significantly higher than that of the control legs (CON) (7.8 %, P<0.05). Meanwhile, in Wistar rats, the LG mass was unchanged. In SD rats, the levels of 70-kDa ribosomal protein S6 kinase (p70S6k) and forkhead box 3a (FOXO3a) phosphorylation in the TRN were significantly greater than those of the CON (2.2- and 1.9-fold, respectively; P<0.05). The expression of muscle ring finger-1 (MuRF1) and muscle atrophy F-box (MAFbx/atrogin-1) in the TRN were significantly lower than those of the CON (0.6- and 0.7-fold, respectively; P<0.05). However, in Wistar rats, there was no significant difference. These results suggest a genetic strain difference in protein metabolism. This phenomenon may be useful for studying individual differences in response to RT., K. Kobayashi ... [et al.]., and Obsahuje seznam literatury
Mutations in troponin T (TNNT2) gene represent the important part of currently identified disease-causing mutations in hypertrophic (HCM) and dilated (DCM) cardiomyopathy. The aim of this study was to analyze TNNT2 gene exons in patients with HCM and DCM diagnosis to improve diagnostic and genetic consultancy in affected families. All 15 exons and their flanking regions of the TNNT2 gene were analyzed by DNA sequence analysis in 174 patients with HCM and DCM diagnosis. We identified genetic variations in TNNT2 exon regions in 56 patients and genetic variations in TNNT2 intron regions in 164 patients. Two patients were found to carry unique mutations in the TNNT2 gene. Limited genetic screening analysis is not suitable for routine testing of disease-causing mutations in patients with HCM and DCM as only individual mutation-positive cases may be identified. Therefore, this approach cannot be recommended for daily clinical practice even though, due to financial constraints, it currently represents the only available strategy in a majority of cardio-centers., M. Jáchymová ... [et al.]., and Obsahuje seznam literatury
Ghrelin is a new endogenous peptide, discovered in 1999 by Kojima et al., as the result of a search for an endogenous ligand for an orphan receptor of known structure and function. Ghrelin is composed of 28 amino acids and is produced mostly by cells of the stomach, hypothalamus, and hypophysis, but it has also been detected in other tissues. Its discovery is related to the development of a new hypothesis regarding the regulation of growth hormone secretion. It is an antagonist of somatostatin. Ghrelin activates the release of growth hormone from the somatotrophic cells of the hypophysis. It participates in the regulation of energy homeostasis, increases food intake, decreases energy output and exerts a lipogenetic effect. Its metabolic effects do not depend on the GH/IGF-I system, but are mediated by the NPY/Y1 and AGRP receptor system. Ghrelin influences the secretion and motility of the gastrointestinal tract, especially the stomach. The presence of ghrelin and its receptors has also been demonstrated in many other tissues. Its function in these tissues has not yet been studied, thus providing many possibilities for further research., M. Rosická, M. Kršek, Z. Jarkovská, J. Marek, V. Schreiber., and Obsahuje bibliografii
Ghrelin and agonists of its re ceptor GHS-R1a are potential substances for the treatment of cachexia. In the present study, we investigated the acute and lo ng-term effects of the GHS-R1a agonist JMV 1843 (H-Aib-DTrp-D-gTrp -CHO) on food intake, body weight and metabolic parameters in lean C57BL/6 male mice. Additionally, we examined stability of JMV 1843 in mouse blood serum. A single subcutaneous injection of JMV 1843 (0.01-10 mg/kg) increased food intake in fed mice in a dose- dependent manner, up to 5-times relative to the saline-treated group (ED 50 =1.94 mg/kg at 250 min). JMV 1843 was stable in mouse serum in vitro for 24 h, but was mostly eliminated from mouse blood after 2 h in vivo . Ten days of treatment with JMV 1843 (subcutaneous administration, 10 or 20 mg/kg/day) significantly increased food intake, body weight and mRNA expression of the orexigenic neuropeptide Y and agouti-related peptide in the medial basal hy pothalamus and decreased the expression of uncoupling protein 1 in brown adipose tissue. Our data suggest that JMV 1843 could have possible future uses in the treatment of cachexia., M. Holubová, ... [et al.]., and Obsahuje seznam literatury
Single unit recordings were made from the motor cortex of conscious cats with glass micropipettes that allowed ionophoretic application of 0.5 M glutamate in 2 M NaCl or 0.5 M ACPD (1S,3R-1-amino-cyclopentane-1,3-dicarboxylic acid, a mGluR agonist) in 2 M NaCl. Activity in response to a 70 dB click (1 ms rectangular pulse to loudspeaker) was studied before, during, and immediately after applying each agent locally as a paired US (90 nA current 570 ms after click for 300 ms in combination with glabella tap). A 70 dB hiss sound was presented 4.4 sec after the click as a discriminative stimulus (DS). CS and DS were presented 10 times initially (adaptation); then CS, US plus tap, and DS (approximately 10 times as conditioning); and then CS and DS (2-10 times to test post-conditioning). Glutamate potentiated the mean, early, 8-16 ms response to the click after conditioning (t=18.2, p<0.0001), but not the baseline activity which decreased from a mean of 17 spk/sec to 7 spk/sec (t=3.71, p<0.001). Baseline activity increased to 31 spk/sec when glutamate was applied during conditioning (t=3.30, p<0.005). ACPD reduced the intermediate, 64-72 ms response to the click after conditioning (t=8.18, p<0.0001), and potentiated the late 104-112 ms response (t=15.4, p<0.0001). Baseline activity was slightly increased after conditioning with ACPD. Saline did not potentiate the response to click. The results indicate that glutamate agonists that differ in their receptor affinities can induce different CRs when used as locally applied USs to condition neuronal responses to a click CS in the motor cortex of cats., Ch. D. Woody., and Obsahuje bibliografii
Primary aldosteronism (PA) is the most common cause of endocrine hypertension with a high frequency of cardiovascular complications. We found in our previous study higher occurrence of metabolic disturbances in patients with idiopathic hyperaldosteronism (IHA) compared to subjects with aldosterone-producing adenoma (APA). The aim of our present study is to evaluate potential differences in the frequency of endorgan damage (arterial stiffness and microalbuminuria) between two main types of PA. The diagnosis of the particular form of PA was based on adrenal venous sampling and/or histopathological examination. We analyzed clinical and laboratory data from 72 patients with PA (36 with IHA, 36 with APA). The arterial stiffness was expressed as the carotid-femoral pulse wave velocity (PWV) and the renal damage as urinary albumin excretion levels (UAE). Patients with IHA had significantly (p<0.03) higher prevalence of metabolic syndrome (17 % in APA, 35 % in IHA), higher triglycerides (1.37±0.71 mmol/l in APA, 1.85±0.87 mmol/l in IHA), lower HDL cholesterol (1.25±0.28 mmol/l in APA, 1.06±0.25 mmol/l in IHA), higher PWV (7.91±1.61 m/s in APA, 8.99±1.77 m/s in IHA) and higher UAE (12.93±2.21 mg/l in APA, 28.09±6.66 mg/l in IHA). It seems that patients with IHA may have a slightly different phenotype compared to APA., Z. Šomlóová ... [et al.]., and Obsahuje seznam literatury
The most frequent hereditary hearing loss is caused by mutations in the GJB2 gene coding for the gap junction beta 2 protein Connexin 26 (Cx26). In contrast to many studies performed in patients with bi-allelic mutations, audiometric studies on heterozygotes are sparse and often contradictory. To evaluate hearing function in heterozygous carriers of the GJB2 c.35delG mutation, audiometry over the extended frequency range and the recording of otoacoustic emissions (OAEs), i.e., transient-evoked OAEs (TEOAEs) and distortion product OAEs (DPOAEs), were performed in a group of parents and grandparents of deaf children homozygous for the GJB2 c.35delG mutation. The comparison of audiograms between control and heterozygous subjects was enabled using audiogram normalization for age and sex. Hearing loss, estimated with this procedure, was found to be significantly larger in GJB2 c.35delG heterozygous females in comparison with controls for the frequencies of 8-16 kHz; the deterioration of hearing in heterozygous men in comparison with controls was not statisticaly significant. A comparison of TEOAE responses and DPOAE levels between GJB2 c.35delG heterozygotes and controls did not reveal any significant differences. The results prove the importance of using audiometry over the extended frequency range and audiogram normalization for age and sex to detect minor hearing impairments, even in a relatively small group of subjects of different ages., D. Groh, ... [et al.]., and Obsahuje seznam literatury